Evaluation of Lead Hepatotoxicity; Histological, Histochemical and Ultrastructural Study

Ahmed M. S. Hegazy, Usama A. Fouad

Anatomy Department, Benha Faculty of Medicine, Benha University, Banha, Egypt.

DOI: 10.4236/fmar.2014.23013                

Abstract

Lead is one of the most well-known naturally occurring environmental heavy metals. This experimental study was designed to evaluate lead induced toxic effects on hepatocytes and lobular architecture as judged microscopically. Material and Methods: This study was conducted in anatomy department, Benha faculty of medicine, Benha University, Egypt from May to October 2013 on 30 normal adult albino rats divided into 3 groups; one control and 2 experimental groups. The experimental groups were given 0.13% lead acetate solution in drinking water for 4 and 8 weeks, respectively. Animals were scarified and livers were removed and used to identify microscopic changes. Specimens were stained with Hematoxylin and eosin, with Masson trichrome stain for study of fibrous tissue and with periodic acid shiff's (PAS) to study the glycogen content. Other specimens were prepared for ultrastructural study. Results: Mild lymphocytic infiltration, vacuolar degeneration and mild increase of periportal fibrosis with mild depletion of glycogen content and partial disappearance of glycogen vacuoles were reported in animals received contaminated water for 4 weeks. Animals maintained for 8 weeks on contaminated water showed hepatic changes in the form of abundant lymphocytic infiltration, increased cellular polymorphism, pyknotic nuclei and areas of cell necrosis with evident moderate periportal fibrosis and marked vacuolar degeneration associated with marked depletion of glycogen content. Ultrastructural study revealed mitochondrial edema, appearance of interstitial inflammatory cells, and appearance of scattered variable sized lead electron-dense inclusion bodies. Conclusion: It could be concluded that chronic exposure to lead imposes a potent toxic effect on liver cells manifested as glycogen depletion, cellular infiltration and liver architecture in the form of initiation of periportal fibrosis that may progress to liver cirrhosis.

Keywords

Lead, Rats, Liver, Light Microscope, Electron Microscope

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Moreira, F.R. and Moreira, J.C. (2004) Effects of Lead Exposure on the Human Body and Health Implications. Revista Panamericana de Salud Pública, 15, 119-129. http://dx.doi.org/10.1590/S1020-49892004000200007
[2]	Meyer, P.A., McGeehin, M.A. and Falk, H. (2003) A Global Approach to Childhood Lead Poisoning Prevention. International Journal of Hygiene and Environmental Health, 206, 363-369.
[3]	White, L.D., Cory-Slechta, D.A., Gilbert, M.E., TiVany-Castiglioni, E. and Zawia, N.H. (2007) New and Evolving Concepts in the Neurotoxicology of Lead. Toxicology and Applied Pharmacology, 225, 1-27. http://dx.doi.org/10.1016/j.taap.2007.08.001
[4]	Ahamed, M. and Siddiqui, M.K.J. (2007) Low Level Lead Exposure and Oxidative Stress: Current Opinions. Clinica Chimica Acta, 383, 57-64. http://dx.doi.org/10.1016/j.cca.2007.04.024
[5]	Jones, A.L. (1982) Anatomy of the Normal Liver. In: Hepatology, Z.D. and Boyer, T.D., Eds., Hepatology. A Text Book of Liver Disease, W.B. Saunders Co, Philadelphia, 3-31.
[6]	Bannister, L.H. (1995) Alimentary System. In: Banister, L.H., Berry, M.M., Collis, P.P., Dyson, M., Dussek, J.E. and Ferguson, M.W., Eds., Grays’s Anatomy, 38th Edition, Churchill Livingstone, London, 1683-812.
[7]	Wilczynska, U., Szeszenia-Dabrowska, N. and Sobala, W. (1998) Mortality of Men with Occupational Lead Poisoning in Poland. Medycyna Pracy, 49, 113-128.
[8]	Sharma, V., Sharma, S., Pracheta and Sharma S (2011) Lead Induced Hepatotoxicity in Male Albino Mice: The Protective Potential of the Hydromeyhanolic Extract of Withania Somnifera. International Journal of Pharmaceutical Sciences Review and Research, 7, 116-121.
[9]	Mahmoudzadeh Sagheb, H.R., Heidari, Z., Barbarestani, M. and Noori Mugahi, M.H. (2004) Ultrastructural Study of Neutrophils in Fetal Rat Spleen Following Lead Intoxication. Yakhteh Medical Journal, 5, 172-177.
[10]	McManus, J. and Mowry, R. (1963) Staining Methods. Histological and Histochemical Harber and Row Inc., New York and London.
[11]	Hotchkiss, R.D. (1948) A Microchemical Reaction Resulting in the Staining of Polysaccharide Structures in Fixed Tissue Preparations. Archives of Biochemistry, 16, 131.
[12]	Nriagu, J.O., Blankson, M. and Ocran, K. (1996) Childhood Lead Poisoning in Africa: A Growing Public Health Problem. Science of the Total Environment, 181, 93-100. http://dx.doi.org/10.1016/0048-9697(95)04954-1
[13]	Srianujata, S. (1998) Lead-The Toxic Metal to Stay with Human. The Journal of Toxicological Sciences, Suppl. 2, 237- 240. http://dx.doi.org/10.2131/jts.23.SupplementII_237
[14]	Sharma, V. and Pandey, D. (2011) Protective Role of Tinospora ordifolia against Lead-Induced Hepatotoxicity. Toxicology International, 17, 12-17. http://dx.doi.org/10.4103/0971-6580.68343
[15]	Clement, G.Y. and Paul, B.T. (2007) N-Acetyl-L-Cysteine Affords Protection against Lead-Induced Cytotoxicity and Oxidative Stress in Human Liver Carcinoma (HepG2) Cells. International Journal of Environmental Research and Public Health, 4, 132-137. http://dx.doi.org/10.3390/ijerph2007040007
[16]	Gunawan, B. and Kaplowitz, N. (2004) Clinical Perspectives on Xenobiotic-Induced Hepatotoxicity. Drug Metabolism Reviews, 36, 301-312. http://dx.doi.org/10.1081/DMR-120034148
[17]	Pal, P.B., Sinha, K. and Sil, P.C. (2013) Mangiferin, a Natural Xanthone, Protects Murine Liver in Pb (II) Induced Hepatic Damage and Cell Death via MAP Kinase, NFkB and Mitochondria Dependent Pathways. PLoS One, 8, Article ID: e56894. http://dx.doi.org/10.1371/journal.pone.0056894
[18]	Bennett, W.M. (1985) lead Nephropathy. Kidney International, 28, 12-20. http://dx.doi.org/10.1038/ki.1985.143
[19]	Corpas, I., Benito, M.J. and Antonio, M.T. (1996) Hepatic and Renal Alterations in Newborn Rats Induced by Prenatal and Early Lactational Exposure to Lead and/or Cadmium. Reviews in Toxicology, 13, 76-82.
[20]	Kertesz, V. and Fancsi, T. (2003) Adverse Effects of (Surface Water Pollutants) Cd, Cr and Pb on the Embryogenesis of the Msallard. Aquatic Toxicology, 65, 425-433. http://dx.doi.org/10.1016/S0166-445X(03)00155-3
[21]	Russo, M.A., Kapoor, S.C. and van Rossum, G.D. (1988) Localization of Lead in the Kidney and Liver of Rats Treated in Vivo with Lead Acetate: Ultrastructural Studies on Unstained Sections. British Journal of Experimental Pathology, 69, 221-234.
[22]	Ellender, G. and Ham, K.N. (1987) Connective Tissue Responses to Some Heavy Metals. I. Sodium Loaded Ion Exchange Beads as a Control: Histology and Ultrastructure. British Journal of Experimental Pathology, 68, 277-289.
[23]	Villa, N.R., Mercau, G., Riera, N.M., Santos, N.S. and Vitalone, H. (1993) Lead: Histopathological Findings in Experimental Contamination. Acta Gastroenterol Latinoam, 23, 159-163.
[24]	Papaioannuo, N., Vlemmas, I., Balaskas, N. and Tsangaris, Th. (1998) Histopathological Lesion in Lead Intoxicated Dogs. Veterinary and Human Toxicology, 40, 203-207.
[25]	Ceruti, R., Ghisleni, G., Ferretti, E., Cammarata, S., Sonzogni, O. and Scanziani, E. (2002) Wild Rats as Monitors of Environmental Lead Contamination in the Urban Area of Milan, Italy. Environmental Pollution, 117, 255-259. http://dx.doi.org/10.1016/S0269-7491(01)00273-1
[26]	Goering, P.L. and Fowler, B.A. (1985) Mechanism of Renal Lead-Binding Protein Reversal of Delta-Aminolevulinic Acid Dehydratase Inhibition by Lead. Journal of Pharmacology and Experimental Therapeutics, 234, 365-371.
[27]	Jarrar, B.M. and Mahmoud, Z.N. (2000) Histochemical Characterization of the Lead Intranuclear Inclusion Bodies. Biological Trace Element Research, 75, 245-251. http://dx.doi.org/10.1385/BTER:75:1-3:245